A perspective into the relationships between amphibian ( Xenopus laevis ) myeloid cell subsets.

Macrophage (M)-lineage cells are integral to the immune defences of all vertebrates, including amphibians. Across vertebrates, M differentiation and functionality depend on activation of the colony stimulating factor-1 (CSF1) receptor by CSF1 and interluekin-34 (IL34) cytokines. Our findings to date indicate that amphibian () Ms differentiated with CSF1 and IL34 are morphologically, transcriptionally and functionally distinct. Notably, mammalian Ms share common progenitor population(s) with dendritic cells (DCs), which rely on fms-like tyrosine kinase 3 ligand (FLT3L) for differentiation while IL34-Ms exhibit many features attributed to mammalian DCs. Presently, we compared CSF1- and IL34-Ms with FLT3L-derived DCs. Our transcriptional and functional analyses indicated that indeed the frog IL34-Ms and FLT3L-DCs possessed many commonalities over CSF1-Ms, including transcriptional profiles and functional capacities. Compared to CSF1-Ms, the IL34-Ms and FLT3L-DCs possess greater surface major histocompatibility complex (MHC) class I, but not MHC class II expression, were better at eliciting mixed leucocyte responses and generating re-exposure immune responses against . Further analyses of non-mammalian myelopoiesis akin to those described here, will grant unique perspectives into the evolutionarily retained and diverged pathways of M and DC functional differentiation. This article is part of the theme issue 'Amphibian immunity: stress, disease and ecoimmunology'.